013 A role for SCF/c-kit signaling in the morphogenesis and cyclic regeneration of hair pigmentation unit

N.V. Botchkareva1, V.A. Botchkarev1, M. Khlgatian1, A.A. Sharov1, B. J. Longley2, and B.A. Gilchrest1 1Dept. of Dermatology, Boston University School of Medicine, Boston, USA; 2Dept. of Dermatology, Columbia University, New-York, USA

Stem cell factor (SCF) and its receptor c-kit are important for melanocyte survival during development, and mutations in these genes result in unpigmented hairs. During hair follicle (HF) morphogenesis, melanocyte precursors migrate into developing HF and give rise to differentiated melanocytes that actively produce and transport pigment into keratinocytes of the hair shaft. Using multi-color confocal microscopy and double immunofluorescence of melanogenic proteins [tyrosinase-related proteins 1 and 2 (TRP1/TRP2), tyrosinase], proliferative marker Ki67, and c-kit receptor, we show that during HF morphogenesis and postnatal cyclic HF regeneration proliferating, differentiating, and melanin-producing melanocytes express c-kit, while presumptive melanocyte precursors do not. During postnatal hair cycle, SCF overexpression in HF epithelium significantly increases the number and proliferative activity of melanocytes, while administration of anti-c-kit antibody dose-dependently decreases hair pigmentation and leads to partially depigmented (gray) or fully depigmented (white) hairs, associated with significant decreases in melanocyte proliferation and differentiation. However, in the next hair cycle the previously treated animals grow fully pigmented hairs with the normal number and distribution of melanocytes. This suggests that melanocyte stem cells are not dependent on SCF/c-kit and when appropriately stimulated can give rise to differentiated progeny that migrate and function normally. Therefore, the blockade of c-kit signaling offers a fully reversible model for hair depigmentation, which might be used for the studies of hair pigmentation disorders.